We and others have recently described the presence of HLA-D region molecules on the surface of normal gut epithelial cells. These Ia bearing epithelial cells appear to function similar to other Ia bearing accessory cells in that they are capable of processing and presenting antigen to immunocompetent T cells. Of note is the finding that use of epithelial cells as accessory cells in these systems appears to result, preferentially, in suppressor cell induction. These findings may have implications in normal mucosal immune responses. In contrast, Ia+ epithelial cells from inflammatory bowel disease tissue do not appear to stimulate T suppressor cells but rather induce a marked T helper response analogous to that seen using monocytes as accessory cells. The goal of this proposal is to characterize interactions of epithelial cells from patients with inflammatory bowel disease and determine the mechanism(s) by which T8+ T cells are not induced. This will be accomplished by analysis of differences between normal and IBD epithelium using monoclonal antibodies, characterization of regulatory mechanisms of Ia expression, and analysis of the role of the Fc delta receptor on normal (and not on IBD) epithelium. These studies can potentially aid in the understanding of pathogenetic mechanisms in IBD and should enhance our understanding of normal mucosal immune responses as well.